Paolillo, Michael and Peters, Stefanie and Schramm, Andrea and Schlossmann, Jens and Feil, Robert (2018) Real-Time Imaging Reveals Augmentation of Glutamate-Induced Ca2+ Transients by the NO-cGMP Pathway in Cerebellar Granule Neurons. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 19 (8): 2185. ISSN 1422-0067,
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Dysfunctions of NO-cGMP signaling have been implicated in various neurological disorders. We have studied the potential crosstalk of cGMP and Ca2+ signaling in cerebellar granule neurons (CGNs) by simultaneous real-time imaging of these second messengers in living cells. The NO donor DEA/NO evoked cGMP signals in the granule cell layer of acute cerebellar slices from transgenic mice expressing a cGMP sensor protein. cGMP and Ca2+ dynamics were visualized in individual CGNs in primary cultures prepared from 7-day-old cGMP sensor mice. DEA/NO increased the intracellular cGMP concentration and augmented glutamate-induced Ca2+ transients. These effects of DEA/ NO were absent in CGNs isolated from knockout mice lacking NO-sensitive guanylyl cyclase. Furthermore, application of the cGMP analogues 8-Br-cGMP and 8-pCPT-cGMP, which activate cGMP effector proteins such as cyclic nucleotide-gated cation channels and cGMP-dependent protein kinases (cGKs), also potentiated glutamate-induced Ca2+ transients. Western blot analysis failed to detect cGK type I or II in our primary CGNs. The addition of phosphodiesterase (PDE) inhibitors during cGMP imaging showed that CGNs degrade cGMP mainly via Zaprinast-sensitive PDEs, most likely PDE5 and/or PDE10, but not via PDE1, 2, or 3. In sum, these data delineate a cGK-independent NO-cGMP signaling cascade that increases glutamate-induced Ca2+ signaling in CGNs. This cGMP-Ca2+ crosstalk likely affects neurotransmitter-stimulated functions of CGNs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE-I; NUCLEOTIDE-GATED CHANNELS; CENTRAL-NERVOUS-SYSTEM; SENSITIVE GUANYLYL CYCLASE; LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; RAT-BRAIN; CELLS; EXPRESSION; MICE; cyclic GMP; calcium; nitric oxide; guanylyl cyclase; cerebellar granule cells; protein kinase; PKG; FRET imaging; transgenic mice |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2020 13:47 |
| Last Modified: | 11 Mar 2020 13:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14123 |
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